Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis., T. Štulc, M. Vrablík, Z. Kasalová, I. Marinov, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
In rats, the basic licking rhythm is generated by the central pattern generator located in the brainstem. Nevertheless, the licking frequency can be regulated between abou 7.5 and 4 Hz by changing the drinking conditions. If these conditions are kept constant, the licking frequency can be influenced only to a minor degree by factors such as deprivation level, type of solution, and phase of the session. The aim of our study was to compare the licking frequency of rats at different levels of vigilance. We investigated spontaneous licking of rats by an electrical lick sensor; parallel behavior monitoring was also performed. Animals kept in a stable environment and showing a lower level of vigilance licked at a rate of 5.96 Hz, fully vigilant rats licked significantly more rapidly at a frequency 6.57 Hz. The fastest rate of licking (6.49 Hz and 6.82 Hz, respectively) was encountered in alert rats under a mild stress caused by the presence of a second animal in the experimental box. The vigilance level is thus another factor affecting the licking rate of rats that should be taken into account in behavioral licking experiments., O. Vajnerová, E. Bielavská, P. Jiruška, G. Brožek., and Obsahuje bibliografii
As traditional risk factors are unable to fully explain the pathogenesis of coronary artery disease (CAD), novel mechanisms became a target of many investigations. Our aim was to study the response of selected markers to physical exercise. High-sensitive C-reactive protein (hs-CRP), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), advanced oxidation protein products (AOPP), soluble receptor for advanced glycation end-products (sRAGE), pregnancy-associated plasma protein A (PAPP-A), E-selectin, vascular endothelial growth factor (VEGF) and B-type natriuretic peptide (BNP) levels were measured in serum of 21 CAD patients and in 22 healthy controls at rest and after exercise bicycle stress test performed up to the maximal tolerated effort. At rest, hs-CRP, AOPP, MMP-9 and BNP were significantly elevated in the CAD patients as compared with controls. In contrast, P-selectin was significantly lower in CAD patients and a tendency to lower levels of sRAGE was noted. After exercise MMP-9 and BNP, increased significantly in both groups. In conclusions, CAD patients have elevated hs-CRP, AOPP, MMP-9 and BNP - novel markers related to cardiovascular risk or left ventricular overload. MMP-9 and BNP increase significantly with exercise in both healthy individuals and CAD patients., V. Danzig ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to determine the effect and mechanism of low concentration of lidocaine on subthreshold membrane potential oscillations (SMPO) and burst discharges in chronically compressed dorsal root ganglion (DRG) neurons. DRG neurons were isolated by enzymatic dissociation method. SMPO, burst discharges and single spike were elicited by whole cell patch-clamp technique in current clamp mode. Persistent Na+ current (INaP) and transient Na+ current (INaT) were elicited in voltage clamp mode. The results showed that SMPO was suppressed and burst discharges were eliminated by tetrodotoxin (TTX, 0.2 μ mol/l) in current clamp mode, INaP was blocked by 0.2 μ mol/l TTX in voltage clamp mode. SMPO, burst discharges and INaP were also suppressed by low concentration of lidocaine (10 μ mol/l) respectively. However, single spike and INaT could only be blocked by high concentration of lidocaine (5 mmol/l). From these results, it is suggested that INaP mediates the generation of SMPO in injured DRG neurons. Low concentration of lidocaine (10 μ mol/l) suppresses SMPO by selectively inhibiting INaP, but not INaT, in chronically compressed DRG neurons., H. Dong, Y.-H. Fan, Y.-Y. Wang, W.-T. Wang, S.J. Hu., and Obsahuje bibliografii a bibliografické odkazy
Previous studies have reported a decreased incidence of delayed graft function after cadaveric transplantation with the use of lidocaine pretreatment of the donor. We evaluated the effects of lidocaine on prolonged cold ischemia and reperfusion injury in a canine model of isolated kidney perfusion (IPK). The purpose of this study was to evaluate the renal function of isolated perfused canine kidneys after 48 h of cold storage with Euro-Collins (EC) solution or EC solution plus lidocaine. Isolated perfused canine kidneys were randomized into four groups which contained six kidneys: I) cold flush with EC solution and immediately reperfused, II) cold flush with EC solution plus lidocaine and immediately reperfused, III) 48 h of cold storage with EC and reperfusion, IV) 48 h of cold storage with EC solution plus lidocaine and reperfusion. The measured renal functions were glomerular filtration rate, urine production, perfusate flow, urinary lactic dehydrogenase (ULDH), Na reabsorptive capacity, and tissue MDA levels. Histological examination was performed after reperfusion. The tubular functions of kidneys preserved with EC solution containing lidocaine were better when compared with the kidneys preserved with EC alone. Tubular injury marker levels (ULDH) in group IV were significantly lower than in group III and lidocaine also reduced lipid peroxidation during reperfusion. This is in agreement with the histological results. The results of the present study can be taken as evidence of the cytoprotective effect of lidocaine, which may therefore be accepted as a useful agent for kidney preservation., N. Erkasap, E. Ates, S. Erkasap, Z. Kaygisiz., and Obsahuje bibliografii
During the early postnatal age environmental signals underlie the development of sensory systems. The visual system is considered as an appropriate system to evaluate role of sensory experience in postnatal development of sensory systems. This study was made to assess the effect of visual deprivation on strategy of arm selection in navigation of radial arm maze. Six-week-old light- (LR, control) and dark-reared (DR) rats were trained for correct choices and adjacent arms tasks. Our results showed that both the LR and DR animals equally selected correct arms. In the adjacent arms task, however, the control group significantly outperformed the DR animals. While the LR males and females displayed some differences in performing the tasks, no sex dependency was found in the performance of the DR group. These findings indicate that the lack of visual experience is likely to influence the strategy selection as well as sex differences. Thus the difference in the performance of LR and DR animals seems to be due to the male rather than female behavior., M. Salami., and Obsahuje bibliografii a bibliografické odkazy
The aim of the study was to char acterize a) the lipofuscin-like pigment (LFP) accumulation (an indicator of ROS production) in the rat heart during early postnatal period and b) possible antioxidative role of selenium. Experimental animals received Na 2 SeO 3 in drinking water during gravidity and up to day 15 post partum . Two fluorophores of LFP in the hearts of 1-, 4-, 7- and 15-day-old rats were evaluated by fluorescent analysis. The highest level of heart/body weight ratio in control rats was observed on day 4, in the Se-supplemented rats on day 7. Cardiac LFP content in controls increased from postnatal day 4, in the hearts of Se-supplemented rats the LFP content increased already from day 1. As compared with the Se-supplemented group the LFP content of control hearts was significantly higher on day 1 but significantly lower on day 4. LFP concentration in control hearts decreased from postnatal day 1 to 4; this decrease was followed by significant increa se until day 7 and decrease to day 15. LFP concentration in the Se-supplemented hearts was the highest on postnatal day 7; it differed from controls on day 1 and 4. Significant changes of LF P suggest an important role of ROS during critical ontogenetic period., I. Ošťádalová, Z. Charvátová, J. Wilhelm., and Obsahuje bibliografii
In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hyperchole sterol emic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6 ±13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterol emia (FH): 5 homozygous, 9 hetero zygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using h emorheopheresis. Immunoapheretic interventions decreased LDL-cholesterol (82 ±1 %), ApoB (73 ±13 %) and even Lp(a) by 82 ±19 %, respectively. Selected non-invasive methods are important for long -term and repeated follow -up. Carotid intima-media thickness showed improvement or stagnation in 75 % of the patients. Biomarkers of endothelial dysfunction such as endoglin (in the control group: 3.85 ±1.25 μ g/l, in lipoprotein apheresis-treated hypercholesterol emic individuals 5.74 ±1.47 μ g/l), CD40 ligand (before lipoprotein apheresis: 6498 ±2529 ng/l, after lipoprotein apheresis: 4057 ±2560 ng/l) and neopterin (before lipoprotein apheresis: 5.7 ±1.1 nmol/l, afte r lipoprotein apheresis: 5.5 ±1.3 nmol/l) related to the course of atherosclerosis, but did not reflect the actual activity of the disease nor facilitate the prediction or planning of therapy. Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other microcirculation disorders via significantly decreased activity of thrombomodulin (p<0.0001), tissue factor (p<0.0001), aggregation of thrombocytes (p<0.0001) and plasma and whole blood viscosity (p<0.0001). In conclusion, lipoprotein apheresis and hemorheopheresis substantially lowered LDL-cholesterol in severe hypercholesterolemia. Our experience with long-term therapy also shows good tolerance and a small number of complications (6,26% non-serious clinical compl.), V. Bláha, M. Bláha, M. Lánská, D. Solichová, L. Kujovská Krčmová, E. Havel, P. Vyroubal, Z. Zadák, P. Žák, L. Sobotka., and Obsahuje bibliografii
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28±35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C>T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms., L. Zlatohlávek, K, Zídková, M. Vrablík, T. Haas, M. Prusíková, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
To investigate lisinopril effect on the contribution of nitric oxide (NO) and KCa channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensi ve WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K Ca channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SKCa and IKCa channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SKCa and BKCa proteins. Lisinopril treatment increased expression of eNOS, SKCa , BKCa channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SKCa and IKCa channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SKCa and IKCa channels is reduced, S. Albarwani, S. Al-Siyabi, I. Al-Husseini, A. Al-Ismail, I. Al-Lawati, I. Al-Bahrani, M. O. Tanira., and Obsahuje bibliografii